Recent development in diffuse optical tomography (DOT) and CCD technology may allow us to achieve high-quality, good-resolution, optical tomographic images, for which advanced 3-dimensional (3D) imaging reconstruction algorithms are inevitably needed. The objective of this proposal is to develop a fast globally convergent reconstruction (GCR) algorithm for 3D tomographic imaging of vascular oxygenation obtained by combining DOT, CGD measurements, and the near infrared spectroscopy (NIRS). With such a superior reconstruction algorithm, which has a capability to handle large data sets and proven mathematically to be of convergence at any complex background, we will be able to accomplish 3D, non-invasive optical imaging as a dynamic monitoring means to investigate microcirculatory dysfunction during ischemic stroke using animal models. The specific aims in the R21 phase are (1) to design and implement a CCD-camera-based, NIRS imaging system suitable for dynamic imaging of cerebral concentrations of oxygenated hemoglobin (HbO) and total hemoglobin (HbT), and (2) to develop and to validate the fast GCR algorithm for 3D tomographic reconstruction of vascular contents and oxygenation based on the CCD/NIR measurements. After success of the initial R21 development, the PI and her collaborators will apply the developed GCR algorithm to the investigation of microcirculatory dysfunction during ischemic stroke using animal models. The specific aims in the R33 phase are: (1) using the developed GCR algorithm with the CCD/NIR measurements to obtain 3D tomographic images of cerebral concentrations of oxygenated hemoglobin, total hemoglobin, and light scattering parameters from the rats in vivo during and after ischemic stroke, (2) to characterize the cerebral-ischemia- induced microvasculature dysfunction identified by the 3D NIR imaging, (3) to determine the effect of a anti- stroke drug on microvasculature dysfunction in the cerebral ischemia model, and (4) to implement an integrated, user-friendly platform/environment for users in academic and medical communities for sharing both (a) our developed 3D GCR algorithm for NIR tomographic imaging and (b) our data-intensive, CCD camera based, NIR spectroscopic readings. The proposed technique and development can be readily applicable to other types of neurological deceases and therapeutic monitoring after its validation. Furthermore, this functional imaging technique will enhance our understanding on dynamics, mechanism, and heterogeneity of ischemic stroke.